Patent GB-966098-A (GB)
Title: Barbiturate derivatives
Inventor: GOLD-AUBERT PHILIPPE
IPC: C07D/
Filed: 1959-11-23
Abstract: The invention comprises (1) compounds of the formula: <FORM:0966098/C1/1> (wherein R4 and R5 are aliphatic hydrocarbon radicals or aryl, aralkyl or heterocyclic groups and the free valency is occupied by a group -CH2.CH(OZ).CH2Hal, -CH2.CH(OZ).CH2 OZ or ZOCH2.CH.CH2Hal, Z being hydrogen or an aliphatic hydrocarbon radical which may be substituted by an alkoxy group or is an aryl or aralkyl group or a group CONY1Y2 in which Y1 and Y2 are hydrogen atoms or alkyl groups, and Hal being a halogen atom) but excluding 5-phenyl-5-ethyl-3-(b , g -dihydroxypropyl)-barbituric acid; (2) compounds of the formulae: <FORM:0966098/C1/2> <FORM:0966098/C1/3> (wherein R1 is a halogen atom or a group OZ and R3 is a barbiturate group of the above structure, or R2 is the barbiturate group and R3 is a halogen atom); and (3) a process for preparing the compounds defined under (1) wherein an appropriate 3-metallo-5-R4-5-R5-barbituric acid is reacted with a halohydrin derivative of the formula R1CH2.CH(R6).CH2R7 (wherein R6 is a halogen atom or a group OZ, R7 is a halogen atom and R1 is a group OZ or, when R6 is a group OZ, a halogen atom) and, when required, the product is reacted with a haloformamide or a carbamyl ester to replace any free hydroxyl groups present by groups OCONY1Y2.  This process may in turn be combined with the preparation of the halohydrin derivatives by reacting epichlorhydrin with a compound HOZ if desired in the presence of a catalyst such as sulphuric acid to give a compound of the formula ZOCH2.CH(OH).CH2bl (Z being other than hydrogen) which may then, if desired, be reacted with a further quantity of alcohol ZOH, a haloformamide or a carbamyl ester or first with a carbamyl halide and then with the amine NHY1Y2. Other starting materials may be prepared by reacting compounds R1CH2.CH(R6).CH2R7\t containing one or two hydroxy groups with carbamyl esters of haloformamides. The dimeric compounds defined under (2) may be prepared by heating the appropriate monomeric compounds of (1) in which OZ is OCONHY1 (Y1 being hydrogen or alkyl) at a high temperature, e.g. 140 DEG C., for several hours. In the products of this dimerization halogen or hydroxyl groups may be replaced by appropriate carbamyloxy and barbiturate groups. In the process defined under (3) when both R6 and R7 are halogen atoms a mixture of products may be formed and then separated, e.g. by solubility or adsorption differences. Examples are given. N-diethyl-chloroformamide is prepared from phosgene and diethylamine. The Provisional Specification describes compounds of the formula: <FORM:0966098/C1/4> in which R1 and R2 are halogen atoms or the group OZ, Z being hydrogen or a substituted or unsubstituted aliphatic hydrocarbon, aryl or aralkyl group or Z is the group CONY1Y2 (Y1 and Y2 being hydrogen atoms or substituted or unsubstituted alkyl groups), or R1 has one of these meanings and R2 is a group of the formula II above (R4 and R5 have the meanings given above but may also be substituted) and in which R3 is halogen (when at least one of R1 and R2 is OCONY1Y2) or a group of the formula II (when neither R1 nor R2 represents such a group).  The compounds of the invention, which are stated to have anticonvulsant, sedative and tranquillising properties, may be made up into pharmaceutical compositions with suitable carriers. They may take the form of solutions, suspensions, capsules, tablets or cachets and may contain dispersing, flavouring, sweetening or wetting agents.